Singlet molecular oxygen in the form of the delta state O2, (1 delta g) has been identified as a potential atmospheric oxidant. Although the ambient levels of O2 (1 delta g) are not well established, recent research indicates that it is sufficiently long lived and, is generated in such concentrations, that it is likely to reach the alveolar region of the lung. It is also possible that singlet oxygen may be formed in situ by a number of mechanisms, e.g., in the hydrolysis of peroxyacetyl nitrate (PAN) and by the reaction of ozone. In the lung singlet oxygen is an agent that can produce subtle chemical alterations of the pulmonary surfactant, alveolar macrophages and the alveolar-pulmonary endothelium which can predispose to various pathological conditions. In this respect it is most likely that singlet oxygen will attack the unsaturated fatty acid moieties of the alveolar phospholipids (lecithins) forming hydroperoxides via the "ene" reaction. Among the possible oxidation products to be expected is malonyl aldehyde which has recently been reported to exhibit carcinogenic activity. Also, the hydroperoxides are known toxins that exert their effects on lungs, causing inflammation, edema and hemorrhaging. The formation of hydroperoxides in the lung and the mechanism by which they act on the tissue of the lung are at the present time unreported. Accordingly, a research program will be proposed that will (1) Investigate the possible involvement of singlet oxygen in chemically modifying pulmonary surfactant and/or alveolar macrophages, (2) Determine the concentration levels of singlet oxygen required to obtain such alterations, (3) Determine the effects of such alterations on normal lung functions, and (4) Identify the chemical species and/or physical alterations producing such changes. A supplementary grant is requested in light of the fact that the techniques for generating and handling singlet molecular oxygen have been demonstrated. It will allow the program to proceed at a more desireable pace, and in the end to accomplish the major goals defined in the original proposal and restated herein.